Clinical validation of a model-based glycaemic control design approach and comparison to other clinical protocols

Abstract

Hyperglycaemia is prevalent in critical care and tight control can reduce mortality from 9-43% depending on the level of control and the cohort. This research presents a table-based method that varies both insulin dose and nutritional input to achieve tight control. The system mimics a previously validated model-based system, but can be used for long term, large patient number clinical evaluation. This paper evaluates this method in simulation using retrospective data and then compares clinical measurements over 15,000 patient hours to validate the models and development approach. This validation thus also validates the in silico comparison to the landmark clinical tight glycaemic control protocols. Overall, an average clinical glucose level is 5.9 ± 1.0 mmol/L, matching simulation, however the overall clinical glucose distribution is slightly tighter than that obtained in simulation, indicating that the retrospective virtual trial design approach is slightly conservative. Finally, the model based approach is shown to have tighter control than existing, more ad-hoc clinical approaches based on the simulation results that qualitatively match reported clinical results, but also show significant variation around the average levels obtained in both the hypoand hyper-glycaemic ranges.